1. Field of the Invention
The present invention relates to solid, film-shaped preparations comprising at least one oily substance for oral administration.
2. Description of the Prior Art
Flat-shaped forms of administration for use in the oral region and on the mucous membranes of the mouth, so-called wafers, are known. U.S. Pat. No. 3,444,858 describes medicament strips based on a gelatine-containing material. Also, medicaments in the form of films were already described at the beginning of the seventies, such as, for example, in the New England Journal of Medicine, 289, 533-535 (1973). The utility model specification DE 24 49 865 describes active pharmaceutical ingredient carriers in the form of films that contain various active ingredients and concentrations of active ingredients.
U.S. Pat. No. 4,128,445 discloses technical solutions for the loading of carrier material with active ingredients. In this connection, the patent addresses the subsequent addition of active ingredient preparations onto prefabricated film-shaped preparations. The document describes loading methods in dry and in moist form that aim at a uniform, subsequent distribution of active ingredient on a layer.
Also known are proposals for active ingredient-loaded films for applications outside the medical field. EP 0 219 762, for example, discloses a water-soluble film of starch, gelatine, glycerine or sorbite that is coated using a roll coating process. In this connection, it is stated therein that such dosage forms may also be produced utilising flavouring substances.
A formulation suited for producing film-shaped flavouring substance-containing preparations is described in EP 0 460 588. A composition of 20 to 60%-wt. film former, 2 to 40%-wt. gel former, 0.1 to 35%-wt. active ingredient or flavouring substance, and not more than 40%-wt. of an inert filler is considered to provide special advantages. Apart from other compounds, polyvinyl alcohol is mentioned as a gel former. It has, however, emerged that the gel-forming properties of polyvinyl alcohol are only to a limited extent compatible with the film formers mentioned in that printed publication. A content of 20 parts by weight, and more, of film former—mostly a sugar derivative, polyethylene glycol, or the like—resulted in a considerable loss of aroma occurring already in the drying of thin layers, which is part of the production process.
Flavouring substance-containing forms of administration for application in the oral region are also known from EP 0 452 446, but this document does not describe any measures to prevent an evaporation of flavouring substances during production and/or storage. As a solution to that problem, DE 196 52 257 discloses individually dosed, film-shaped forms of administration which rapidly disintegrate upon contact with a liquid and which can be produced avoiding loss of active ingredients during their production and storage. These film-shaped forms of administration have an internal, liposoluble phase in the form of droplets that contain the flavouring substance and are present in an outer, solid but water-soluble phase, with the outer phase comprising, relative to the water-free portions, at least 40%-wt. of polyvinyl alcohol, up to 30%-wt. of a surface-active substance and 0.1 to 30%-wt. of an internal phase, relative to the outer phase.
Film-shaped preparations for application in the mouth are already available on the market as active ingredient-containing or flavouring substance-containing forms of administration. For example, wafer-thin strips that leave a cool, breath-fresh taste sensation on the tongue without sucking or chewing are sold in the flavours “Peppermint”, “Wild-Mint” and “Lemon-Frost” by the company Wrigley under the names ECLIPSE FLASH®, or by the company Pfizer in the flavours “COOL MINT®”, “FRESHBURST®”, Cinnamon and “Fresh Citrus” under the trade mark Listerine POCKETPAKS®.
Hydrophilic, film-forming polymers are used to achieve a rapid disintegration or rapid dissolution behaviour of film-shaped preparations on contact with saliva.
However, if oily substances are to be administered with a film-shaped preparation that rapidly dissolves in the oral cavity, the differing properties of the matrix (=hydrophilic film-forming polymer) and of the oily substance (hydrophobic) which is to be incorporated in the matrix cause problems.
Since hydrophilic polymers usually only have a low absorption capacity for lipophilic substances, the amount of oily substance with which hydrophilic films can be loaded is limited. This limitation becomes particularly apparent if larger amounts of an oily liquid are to be processed with a hydrophilic polymer into a film since in that case the oily substance exudes, for example due to phase separation occurring during the preparation of the compound (separation of the oil-in-water emulsion) or, later, during storage of the films.
However, for certain applications it is necessary to accommodate a large amount of an oily substance in a film-shaped preparation. For example, to achieve a desired therapeutic effect it may be necessary to load the film with a large amount of an oily active ingredient. For example, for the active ingredient simethicone, which is used as a carminative, a dose of about 80 mg is indicated as therapeutically effective. This amount is administered, for example, by means of known liquid forms of administration. For an administration by means of a film-shaped preparation rapidly disintegrating in the mouth, this amount would however be too large to be able to produce stable films.
To avoid the stability problems occurring during the loading of a hydrophilic film with a hydrophobic substance, surface-active substances are usually added to a material consisting of a hydrophilic polymer and a hydrophobic, liquid or oily substance, i.e. tensides or emulsifiers which reduce the interfacial surface tension between the phases. U.S. Pat. No. 6,177,096, for example, discloses the production of film-shaped forms of administration with addition of surface-active substances.
However, the use of surface-active substances in oral preparations is frequently undesirable because it can have a negative impact on the taste sensation by causing a soapy foreign taste. In addition, the amount of the surface-active substances added to the film-forming polymer limits the possible total loading of the film with oily substance if the surface-active substances do not themselves possess film-forming properties as well.